Prognosis Remains Unclear After Early Sickle Cell Symptoms

Action Points

Explain to parents of children with sickle cell disease that the illness is highly variable from person to person, and there is little understanding of the variation.

Note that this study suggests that some major symptoms of the disease, even when seen early in childhood, do not predict a poor outcome later in life.

DALLAS, Jan. 30 -- Serious symptoms of sickle cell disease in childhood don't imply a greater risk of premature stroke or death for patients as they grow up, according to researchers here.

The findings, from a long-term retrospective study of more than 200 children with two forms of sickle cell disease, leave physicians without useful prognostic guidelines, said Charles Quinn, M.D., of the University of Texas Southwestern Medical Center.

Until there's a deeper understanding of the disease course, Dr. Quinn and colleagues reported in the January issue of Blood, intensive disease-modifying therapy in young children shouldn't be undertaken on the basis of a few episodes of early pain or swelling of the fingers.

Indeed, they said, the only early vaso-occlusive symptom that appeared to have predictive value was acute chest syndrome (ACS). This was defined as acute pulmonary illness in a patient with sickle cell disease, characterized by a new radiographic pulmonary infiltrate and some combination of fever, hypoxemia, thoracic pain, and signs and symptoms of respiratory illness.

Children who have early episodes of ACS, the researcher found, are likely to have more of them as they grow up than do other children with sickle cell disease.

Two other common early symptoms -- dactylitis, or painful swelling of the fingers, and non-dactylitis pain -- did not predict any future complication, the researchers said.

The findings make it difficult to counsel parents of babies with sickle cell disease about what they can expect, Dr. Quinn said.

"We can't give them very much in the way of specifics, exactly what this child will likely go through, or what to expect from the disease in the future," he said.

The researchers analyzed medical records of 244 children with sickle cell disease, members of the Dallas Newborn Cohort, who had been treated in hospital for one of the three early symptoms within the first year of life.

Children in the study had either sickle cell anemia or sickle-Î²0-thalassemia. Median length of follow-up was 12.1 years.

The researchers studied the associations between the three early symptoms and later adverse events, including death and stroke, use of disease-modifying therapy, and hospitalizations for pain events and ACS.

Only ACS was a significant predictor in multivariate analysis - children with early ACS were twice as likely as other children to have later ACS episodes. The odds ratio was 2.23, with a 95% confidence interval from 1.52 to 3.29, which was statistically significant at P<0.001.

It was surprising that dactylitis did not predict any later events, Dr. Quinn said. "That finding in particular is at odds with other studies that showed that early dactylitis does predict later adverse outcomes," he said.

But in particular, none of the three symptoms was associated with an increased risk of stroke or death, he and colleagues reported. "Fortunately, both are becoming rare in children, given the diminishing mortality from invasive bacterial infection and splenic sequestration, as well as the prevention of first stroke using transcranial Doppler ultrasonography to direct the initiation of chronic red blood cell transfusions," they wrote.

The authors noted several limitations of this retrospective study. "We studied only hospitalizations for pain, dactylitis, and ACS," they wrote. "Many episodes of pain and dactylitis are managed only at home and not in a hospital or an outpatient facility, and we did not systematically record these outpatient events."

"There are numerous clinical, laboratory, and psychosocial factors that could influence outcomes in sickle cell disease that we did not consider here. Even though we nominally controlled for multiple comparisons, some of the statistically significant associations we found may still have been type I errors."

The research was partly supported by the National Institutes of Health. The researchers reported no financial conflicts.

Reviewed by Zalman S. Agus, MD Emeritus Professor at the University of Pennsylvania School of Medicine